肿瘤免疫治疗的新思路课件.ppt

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1、ANewApproachtoCancerImmunotherapy肿瘤免疫治疗的新思路1)Slowertumorgrowth(抑制>90%)2)Tumorsshrink(肿瘤体积减小,少见)3)Tumorsdisappear(治愈,极少)治疗0-30days5x105tumorcellsHowtodoantitumorexperiments如何做肿瘤治疗效果试验32-dayMCA207beforetreatmentOneweekafterCy+IL-12TwoweeksafterCy+IL-12ThreeweeksafterCy+IL-12Fourweeksaft

2、erCy+IL-12FiveweeksafterCy+IL-12SixweeksafterCy+IL-12PotentiationofCy-inducedCancerRegressionbyIL-12通过白介素12提高化疗的抗肿瘤效果noRxCyaloneIL-12aloneCy+IL-12Day-18peritonealMCA207tumors18天腹腔实体MCA207肿瘤Day-14experimentallungmetastases14天静脉注射建立的肺扩散肿瘤模型AntitumoreffectsofCy+IL-12inMCA207i.p.andi.v.mo

3、delsCy+IL-12在腹腔及肺扩散肿瘤模型中的治疗效果routeofinoculation接种treatment(startatday)治疗（起始时间）curerate(survivaldays)治愈率（存活天）i.p.腹腔i.p.腹腔i.v.肺扩散None无Cy+IL-12(18)Cy+IL-12(14)0/5(20-27)0/5(21-31)5/5(>90)8/8(>90)i.v.肺扩散None无EffectsofIL-12andCy+IL-12intheSa1ascitestumormodelIL-12和Cy+IL-12在Sa1腹水肿瘤模型中的治疗效果

4、100%50%0%saline生理盐水IL-12CyCy+IL-12010203040tumor接种treatment治疗survival存活率days天数TherejectioninducedbyIL-12/Cy+IL-12isassociatedwithastrongTcellresponse与肿瘤排斥所对应的强免疫反应CD4CD8before之前after之后TumorrejectionismediatedbyaTh1response抗肿瘤作用需要Th1型T细胞参与host宿主curerate治愈率Normal正常TCRbKOT细胞受体敲除Nude裸鼠IFN

5、-gKO咖玛干扰素敲除IL-4KO白介素-4敲除10/100/30/200/2010/10DoesCy+IL-12workonothertumormodels?环磷酰胺加白介素是否对所有肿瘤有效？Respondingtumors:C57B/6:MC203,MCA205,MCA207,FBL-3BALB/c:CT26,CSA1M,OV-HMA/J:Sa1Non-respondingtumors:C57BL/6:MCA101,B16,LLC,Pan02,EL-4BALB/c:4T1,S180Question问题Ifimmunotherapyisabletoeradic

6、atelate-stagelargetumorburdens,whatistheproperconditionforit?如果免疫疗法有可能治愈晚期癌症，条件是什么？DoesCy+IL-12workonothertumormodels?环磷酰胺加白介素12是否对所有肿瘤有效？Condition#1：Pre-existingimmunity条件一：预存免疫Whatispre-existingimmunity?什么是预存免疫？Antigen－specificrecognitionoftumorbythehostimmunesystem宿主对肿瘤抗原有特异性识别Thei

7、mmunesystemhasrespondedtotheexistingtumorpriortotherapystart宿主免疫系统在治疗之前已经对肿瘤有攻击Thehostresponsetothetumoriscell-mediatedTh1type宿主对肿瘤的应答属于Th1型细胞反应Experimentalprocedureforadoptivecelltransfer体细胞转导试验步骤donor供体tumorvaccine瘤苗tumorchallenge肿瘤接种tumor-free排斥接种recipient受体tumorchallenge肿瘤接种14dayT

8、cellt